Low-dose VS High-dose IV Cyclophosphamide for Proliferative LN in Children

Phase 4

Terminated

• Conditions: Renal Insufficiency; Infection
• Interventions: Drug: Low-dose intravenous cyclophosphamide; Drug: High-dose intravenous cyclophosphamide

• Registration Number: NCT01861561
• Lead Sponsor: Mahidol University

Brief Summary

Proliferative lupus nephritis (LN)is the predominant cause of morbidity and mortality in juvenile Systemic Lupus Erythematosus (SLE). Induction therapy with high-dose intravenous cyclophosphamide can improve renal outcomes, but considerably associated with infection. Although severe infection is the significant complication related to poorer prognosis for juvenile SLE patients in Asia, cyclophosphamide is still commonly used as the drug of choice for severe lupus nephritis. Euro-Lupus Nephritis Trial demonstrated low-dose intravenous cyclophosphamide regimen followed by azathioprine achieved good clinical results comparable with obtained high-dose regimen. There was lower number of severe infection episodes, but no significant difference. Recent studies applied low dose of cyclophosphamide (500 mg/m2/dose or 500 mg/dose)in young patients and showed good renal response. Low-dose intravenous cyclophosphamide regimen might promote non-inferior renal remission whereas decrease risk of serious infection and improve overall patient outcomes.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-05-19
• Study First Submitted QC: 2013-05-21
• Study First Posted: 2013-05-23
• Primary Completion: 2019-05
• Study Completion: 2019-05
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-02
• Last Update Posted: 2020-09-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Child up to 15 years of age who fulfilled the 1997 updating the American College of Rheumatology revised criteria for the classification of SLE and his or her renal biopsy reveals lupus nephritis class III or IV regarding to International Society of Nephrology/Renal Pathology Society revision on the classification of the lupus nephritis.

Exclusion Criteria

• patient who has prior renal insufficiency due to chronic kidney disease other than lupus nephritis
• patient who has the history of cyclophosphamide hypersensitivity
• patient who has prior cyclophosphamide or mycophenolate mofetil administration within 6 months
• patient who is pregnant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-dose intravenous cyclophosphamide	Low-dose intravenous cyclophosphamide	Low-dose intravenous cyclophosphamide 500 mg/m2/dose every 4 weeks/months for 7 doses. Total duration is 6 months for the induction treatment.
High-dose intravenous cyclophosphamide	High-dose intravenous cyclophosphamide	High-dose intravenous cyclophosphamide 1,000 mg/m2/dose, the first dose will be started with 500 mg/m2/dose and steped up to 750 mg/m2/dose for the second dose. Then the dosage will be increased to 1,000 mg/m2/dose for the third dose and continued the dosage through the seventh dose. Total duration is 6 months for the induction treatment.

Primary Outcome Measures

Name	Time	Method
renal response	at 6 months of the treatment	3 main renal parameters: renal function(eCCl),proteinuria(spot urine protein/creatinine ratio, UPCR), and urine sediment (rbc,wbc,and casts) 'renal remission'; * complete- normal renal function, UPCR\<0.2, and normal urine sediment(rbc\<5,wbc\<5/HPF,and no cast); * partial- at least 50%improvement in 2 main parameters with UPCR \<= 1.0 and without worsening of remaining main parameter

Secondary Outcome Measures

Name	Time	Method
infection	within 6 months	infectious episode classified in 3 levels; * mild infection - the infection that is not serious and the patient could be treated with oral antimicrobial agent in outpatient clinic; * moderate infection - the infection that the patient need admission or intravenous antimicrobial agent; * serious infection - the infection that the patient is critically ill and need ICU care

Trial Locations

Locations (1)

Nephrology division, Department of Pediatrics, Siriraj Hospital; 🇹🇭 Bangkoknoi, Bangkok, Thailand